Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection.

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.

Developmental plasticity of endocrine disorders in obesity model primed by early weaning in dams.

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRß3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

Endocrine manifestations of Langerhans cell histiocytosis diagnosed in adults.

Langerhans cell histiocytosis (LCH) is a rare granulomatous disease of unknown etiology. We retrospectively reviewed data from four patients (3 males and 1 female), mean age 33.5 years old (range: 21-40), with histopathological diagnosis of LCH. All of them presented with symptoms suggestive of endocrine involvement. The main complaint was goiter in two patients and polyuria and polydipsia in three. Before the LCH diagnosis, two patients had unevaluated symptoms of diabetes insipidus (DI) and hypogonadism. The mean time from symptoms onset to diagnosis was 6.25 years (range: 2-13). Histopathological diagnosis was established by total thyroidectomy (TT) biopsy in two patients, skin lesion biopsy in one, and pituitary stalk biopsy in the other. In the two-first patients, surgery was indicated after the fine-needle aspiration biopsy (FNAB) showed a false positive result of differentiated thyroid carcinoma and immunohistochemistry was used for diagnosis confirmation. Three cases were treated with chemotherapy; one of them had already received radiation therapy on the hypothalamic-pituitary region, developing post-radiation hypopituitarism.

Transtorno del crecimiento en el niño y adolescente con diabetes mellitus tipo I

Los efectos de la diabetes mellitus tipo 1 sobre el crecimiento y desarrollo de niños y adolescentes son aún controversiales. Algunos grupos de investigadores afirman que la diabetes en la edad pediátrica va a alterar el crecimiento de los niños, independiente del grupo de control metabólico y otros, incluyendo nuestro grupo, hemos demostrado que el paciente con un llamado "mal control" metabólico con hiperglicemia crónica reflejadas por niveles de hemoglobina glicosilada (HbA1C) elevados, van a presentar una disminución de la velocidad de crecimiento y por tanto terminan con una talla final más baja que su potencial genético. El objetivo de este trabajo es realizar un análisis del efecto que tiene la diabetes sobre la fisiopatología de los factores de crecimiento y como repercuten los mismos sobre las anormalidades que se presentan en la clínica y la auxología del niño y adolescente con diabetes mellitus tipo 1

The effect of type 1 diabetes mellitus on the growth and development of children and adolescents remains controversial. Some groups of investigators have reported that diabetes during the pediatric age will alter the growth of children, independently of the degree of metabolic control, while others, including our group, have demonstrated, that what is called a “poor metabolic bolic”control, with chronic hyperglycemia reflected by elevated HbA1C, will produce a decrease in growth velocity that will end in subjects with short stature for their genetic potential. The aim of this study is to analyze the effect that diabetes has on the physiopathology of growth factors and the role they play on the clinical and auxiological abnormalities that are seen in children with type 1 diabetes mellitus

Endocrine disorders in pediatric - onset Langerhans Cell Histiocytosis.

Langerhans Cell Histiocytosis (LCH) is a rare disorder with a great variety of clinical manifestations. The purpose of this retrospective study was to evaluate the pattern and the long-term course of clinical, laboratorial and radiological findings in pediatric-onset LCH. We reviewed 46 children with histological diagnosis of LCH. Ten children (22%) showed endocrine disorders. Central diabetes insipidus (DI) was observed in all ten patients; GH deficiency was confirmed in four and hypogonadism in two children. There were no adrenal, prolactin or thyroid axis abnormalities. Obesity was observed in three patients. Eight patients showed soft tissue infiltration and five bone involvement. The MRI showed a lack of posterior pituitary bright spot in all DI patients; infundibular infiltration (II) associated or not with sellar or supra-sellar mass was observed in 4 patients. We conclude that the investigation of LCH, a multi-systemic disease, should include central nervous system images. The presence of II and/or DI should raise the diagnosis of LCH. Complete endocrine evaluation, allowing an early hormone therapy, is required to obtain a better quality of life in children with LCH.

Receptores acoplados à proteina G: implicaçöes para a fisiologia e doenças endócrinas / Connect receptors to G protein: implications for the physiology and endocrine diseases

A maioria dos hormônios polipeptídicos e mesmo o cálcio extracelular atuam em suas células-alvo através de receptores acoplados á proteína G (GPCRs). Nos últimos anos, tem sido frequente a identificação e associação causal de mutações em proteínas G e em GPCRs com diversas endocrinopatias, como diabetes insipidus nefrogênico, hipotiroidismo familiar, puberdade precoce familiar no sexo masculino e nódulos tiroidianos hiperfuncionantes. Nesta revisão, abordamos aspectos referentes ao mecanismo de transdução do sinal acoplado à proteína G, e descrevemos como mutações em GPCRs podem levar a algumas doenças endócrinas. Finalmente, comentamos a respeito das implicações diagnósticas e terapêuticas associadas com o maior conhecimento dos GPCRs.